Horm Metab Res 2024; 56(06): 405-418
DOI: 10.1055/a-2226-3971

Revealing Melatonin’s Mysteries: Receptors, Signaling Pathways, and Therapeutics Applications

Kulsoom Kulsoom
1   Department of Biochemistry, Bahauddin Zakariya University, Multan, Pakistan
2   School of Basic Medical Sciences, Xi’an Jiaotong University, Xian, China
Zainab Saba
3   Department of Optometry, Khwaja Fareed University of Engineering & Information Technology, Rahim Yar Khan, Pakistan
Shabab Hussain
4   Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, Universita degli studi di Messina, Messina, Italy
Samra Zahra
5   Department of Biosciences, COMSATS University Islamabad, Pakistan
Maria Irshad
6   Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy
Muhammad Saeed Ramzan
7   Department of Pharmacology, The Islamia University of Bahawalpur, Bahawalpur, Pakistan
› Author Affiliations


Melatonin (5-methoxy-acetyl tryptamine) is a sleep-inducing hormone, and the pineal gland produces it in response to the circadian clock of darkness. In the body, MT1 and MT2 receptors are mostly found, having an orthosteric pocket and ligand binding determinants. Melatonin acts by binding on melatonin receptors, intracellular proteins, and orphan nuclear receptors. It inhibits adenyl cyclase and activates phospholipase C, resulting in gene expression and an intracellular alteration environment. Melatonin signaling pathways are also associated with other intracellular signaling pathways, i. e., cAMP/PKA and MAPK/ERK pathways. Relative expression of different proteins depends on the coupling profile of G protein, accounting pharmacology of the melatonin receptor bias system, and mediates action in a Gi-dependent manner. It shows antioxidant, antitumor, antiproliferative, and neuroprotective activity. Different types of melatonin agonists have been synthesized for the treatment of sleeping disorders. Researchers have developed therapeutics that target melatonin signaling, which could benefit a wide range of medical conditions. This review focuses on melatonin receptors, pharmacology, and signaling cascades; it aims to provide basic mechanical aspects of the receptor’s pharmacology, melatonin’s functions in cancer and neurodegenerative diseases, and any treatments and drugs designed for these diseases. This will allow a basic comparison between the receptors in question, highlighting any parallels and differences that may exist and providing fundamental knowledge about these receptors to future researchers.

Publication History

Received: 04 August 2023

Accepted after revision: 11 December 2023

Accepted Manuscript online:
11 December 2023

Article published online:
19 February 2024

© 2024. Thieme. All rights reserved.

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Rüdigerstraße 14, 70469 Stuttgart, Germany

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